Inclusion Criteria:

1. Greater or equal to 18 years of age.
2. Surgically incurable, metastatic disease from proven colon or rectal adenocarcinoma.
3. Life expectancy of at least 3 months.
4. Histologically confirmed metastatic disease. Histological confirmation may be waived if needle biopsy presents a significant risk to the subject and the clinical setting is clinically consistent with metastasis of colorectal cancer, e.g. surgical findings at laparotomy, or positive PET scan, synchronous histologically confirmed primary tumor with typical metastatic pattern (stage D disease). Waiver can only be granted by the Sponsor, and these cases will be kept to less than 10% of the total study population.
5. Measurable disease. At least one unidimensionally measurable lesion with a diameter ≥10 mm using spiral CT scans (use of spiral CT must be documented in medical records and used consistently throughout the study) or ≥20 mm using conventional CT or MRI scans.
6. No prior systemic chemotherapy or immunotherapy for metastatic or advanced local disease. However patients may have had radiosensitizing doses of fluoropyrimidines (only 5-FU or capecitabine, with or without leucovorin or levamisole is permitted) if completed 6 months prior to treatment on this protocol. No prior irinotecan or oxaliplatin in combination with radiotherapy is allowed.
7. Prior adjuvant therapy is allowed if completed more than 6 months prior to treatment on this protocol. Regimens which included oxaliplatin and irinotecan are allowed.
8. ECOG Performance Status is 0-2 or Karnofsky performance level of 100-70.
9. Willing and able to provide written informed consent.

Exclusion Criteria:

1. Any prior exposure to bevacizumab.
2. A known intolerance to fluoropyrimidine (5-FU, capecitabine, floxuridine, UFT) therapy suggestive of dihydropyrimidine dehydrogenase (DPD) deficiency.
3. Use of the following drugs are not permitted on the protocol: sorivudine (or other nucleoside analogue), or Brivudin™ (or other DPD inhibitor).
4. Pregnancy or lactation. Women with a positive (or no) serum or urine pregnancy test within 15 days of Cycle 1 Week 1. Women must have been amenorrheic for at least 12 consecutive months to be considered to lack potential for child bearing.
5. If sexually active and of child-bearing potential, failure to agree to use adequate contraception during this study and for 60 days after discontinuation of study medication.
6. A concurrent infection, including diagnoses of FUO and evidence of possible central line sepsis (subjects must be afebrile at the start of therapy).
7. Any unstable oncologic emergency syndromes: superior vena cava syndrome, rising bilirubin needing stent placement, spinal cord compression, active bleeding, etc.
8. History of CNS metastasis, or other brain tumor, or history of stroke.
9. Radiation therapy within 6 weeks of Cycle 1 Week 1, or any radiation therapy which encompasses target lesions selected for this study unless those lesions have documented progression of disease.
10. Major surgery, open biopsy, or significant traumatic injury within 4 weeks of Cycle 1 Week 1, or anticipated need for major surgical procedure during the course of the study.
11. Fine needle aspiration or placement of a central line catheter within 7 days of Cycle 1 Week 1.

12. Inadequate bone marrow, liver or kidney function defined as:

    • Serum creatinine more than 1.5 times the upper limit of normal,
    • Urine protein to creatinine ratio >1,
    • Serum bilirubin > 2 times the upper limit of normal,
    • ANC < 1.5 x 109/L,
    • Hemoglobin < 9.0 g / dL
    • Platelet count < 90 x 109/L,
    • SGOT (AST) and SGPT (ALT) more than 3 times the upper limit of normal, or more than 5 times the upper limit of normal for subjects with documented liver metastases.
13. Myocardial infarction, transient ischemic attack, cerebral bleeding, translumenal cardiac angiography or cardiac stent placement or other arterial thrombotic event within 12 months prior to Cycle 1 Week 1.
14. Active, clinically significant cardiovascular or symptomatic arterial peripheral vascular disease [e.g., uncontrolled hypertension, congestive heart failure, claudication, unstable angina, symptomatic cardiac arrhythmia, or New York Heart Association (NYHA) Class 2 or greater].
15. Presence of serious non-healing wounds, gastro-duodenal ulcers active by endoscopy, gastro-intestinal perforation or intra-abdominal abscess, skin ulcers, or bone fractures.
16. INR >1.5 unless on therapeutic doses of oral anticoagulants (e.g. warfarin). If so, must have an in-range INR (usually between 2-3) on a stable dose of drug.
17. Participation in another experimental drug study within 4 weeks prior to Cycle 1 Week 1.
18. Known or suspected anaphylaxis reaction to leucovorin or any allergic reaction to a drug which, in the opinion of the Investigator, suggests an increased potential for a hypersensitivity to CoFactor or other study drug including excipients.
19. Presence of organ allograft requiring immunosuppressive therapy.
20. Unwilling or unable to comply with the study protocol or history of psychiatric disability judged by the investigator to preclude granting of informed consent.