This is a randomized, placebo-controlled, double-blind study of GDC-0449 added to biochemotherapy standard-of-care regimens for metastatic CRC, with treatment until disease progression. Patients will receive either FOLFOX or FOLFIRI chemotherapy with bevacizumab. The decision of which regimen (FOLFOX or FOLFIRI) to use will be made by the treating physician and patient. Patients will be randomized to receive GDC-0449 or placebo and will be stratified based on the chemotherapy regimen chosen and whether or not Response Evaluation Criteria in Solid Tumors (RECIST) measurable disease is present at baseline.

Inclusion Criteria:

• Age ≥ 18 years
• Histologically confirmed metastatic colorectal cancer (CRC)
• Representative tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides, with an associated pathology report, must be confirmed to be available and requested at any time prior to entry of study
• ECOG performance status 0 or 1
• Adequate hematopoetic capacity
• Adequate hepatic function
• Adequate renal function
• Use of an effective method of barrier contraception (for women of childbearing potential)
• Signed informed consent

Exclusion Criteria:

• Prior chemotherapy for metastatic CRC or adjuvant chemotherapy for CRC within the prior 6 months
• Clinically suspected or confirmed CNS metastases or carcinomatous meningitis
• Major surgical procedure within 4 weeks prior to Day 1
• Pelvic radiation within 2 weeks prior to Day 1
• Wound dehiscence requiring intervention, gastrointestinal perforation, or bowel obstruction
• Pregnancy or lactation
• Uncontrolled medical illnesses including the following: infection requiring intravenous (IV) antibiotics; congestive heart failure not controlled with medication; hypertension not controlled with medication
• Thromboembolic disease
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications