OBJECTIVES: I. Compare the efficacy of fluorouracil and leucovorin calcium with and without bevacizumab, in terms of duration of survival, objective response rate, duration of response, time to disease progression, and change in quality of life, in patients with previously untreated metastatic colorectal cancer. II. Compare the safety of these regimens in these patients. III. Assess the safety and preliminary efficacy of bevacizumab combined with irinotecan in these patients. IV. Assess the pharmacokinetics of irinotecan in these patients.

OUTLINE: This is a randomized, double-blind, active-controlled, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1 or higher), site of primary disease (colon vs rectum), and number of metastatic sites (1 vs more than 1). Patients are randomized to one of two treatment arms. Arm I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 1 hour weekly for the first 6 weeks of each 8 week course. Study drug, bevacizumab is administered IV over 30-90 minutes every 2 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive leucovorin calcium and fluorouracil as in arm I and placebo IV over 30-90 minutes every 2 weeks. Treatment continues for up to a total of 48 doses of bevacizumab or a maximum of 96 weeks of therapy. Patients on arm I who have disease progression may continue bevacizumab with or without irinotecan IV over 90 minutes weekly for 4 weeks, with courses repeating every 6 weeks. Patients on arm II who have disease progression may not receive second-line bevacizumab. Patients on either arm who have disease progression may receive irinotecan alone as second-line treatment. Quality of life is assessed every 3-5 weeks. Patients are followed every 4 months for survival.

PROJECTED ACCRUAL: A total of 200 patients (100 per arm) will be accrued for this study.

DISEASE CHARACTERISTICS: Histologically confirmed, previously untreated, metastatic colorectal carcinoma Bidimensionally measurable disease (minimum of two lesions) Not an optimal candidate for first-line irinotecan Must meet at least one of the following criteria: Age 65 years or over ECOG performance status 1-2 Albumin no greater than 3.5 g/dL Prior radiotherapy to the abdomen or pelvis No CNS disease (e.g., primary brain tumor, seizures not controlled with standard therapy, or any brain metastases) No clinically detectable ascites

PATIENT CHARACTERISTICS: Age: See Disease Characteristics 18 and over Performance status: See Disease Characteristics ECOG 0-2 Life expectancy: More than 3 months Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count greater than 75,000/mm3 Hemoglobin at least 9 g/dL (transfusion allowed) No bleeding diathesis or coagulopathy Hepatic: See Disease Characteristics Bilirubin no greater than 2.0 mg/dL AST/ALT no greater than 2.5 times upper limit of normal (ULN)(less than 5 times ULN if liver metastases present) INR less than 1.5 Renal: No history of proteinuria No clinically significant impairment of renal function Creatinine no greater than 2.0 mg/dL Cardiovascular: No uncontrolled hypertension, myocardial infarction, or unstable angina within the past year No New York Heart Association class II or higher congestive heart failure within the past year No serious cardiac arrhythmia requiring medication or grade II or higher peripheral vascular disease within the past year Other: Able to tolerate CT scan contrast dye Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 5 years except basal cell carcinoma of the skin No serious nonhealing wound, ulcer, significant traumatic injury, or bone fracture No concurrent active infection requiring parenteral antibiotics No metabolic dysfunction or other medical condition that would preclude study

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy for colorectal cancer No concurrent immunotherapy Chemotherapy: See Disease Characteristics At least 12 months since prior adjuvant fluoropyrimidines in combination with leucovorin calcium and/or levamisole No other prior chemotherapy No concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics No prior radiotherapy to target lesions At least 12 months since prior administration of fluoropyrimidines as a radiosensitizer during pelvic radiotherapy for rectal cancer completed less than 12 months prior to study At least 14 days since prior radiotherapy No concurrent radiotherapy Surgery: At least 28 days since prior major surgery At least 7 days since prior fine needle aspiration No concurrent open biopsy or anticipated need for major surgery Other: At least 10 days since prior chronic use of oral or parenteral anticoagulants (except as needed to maintain patency of indwelling IV catheters) or thrombolytic agents At least 28 days since participation in other experimental drug study No concurrent oral or parenteral anticoagulants (except as needed to maintain patency of indwelling IV catheters) or thrombolytic agents No concurrent chronic daily aspirin or nonsteroidal anti-inflammatory medications known to inhibit platelet function