This is a Phase II, multicenter, randomized, double-blind, placebo-controlled trial designed to estimate the efficacy of MEGF0444A treatment to disease progression, combined with oxaliplatin + folinic acid + 5-Fluorouracil (mFOLFOX-6) + bevacizumab therapy in participants with metastatic colorectal cancer (CRC).

Inclusion Criteria:

• Histologically or cytologically confirmed CRC not amenable to potentially curative resection with at least one measurable metastatic lesion, as defined by RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate hematologic and end organ function
• For female participants of childbearing potential and male participants with partners of childbearing potential, agreement to use a highly effective form of contraception and to continue its use for 6 months after the last dose of study treatment
• Negative serum pregnancy test within 7 days prior to starting study treatment in premenopausal women and women less than (<) 2 years after the onset of menopause

Exclusion Criteria:

Disease-specific exclusions

• Any prior systemic therapy (including chemotherapy, antibody therapy, tyrosine kinase inhibitors, radiotherapy, immunotherapy, hormonal therapy or investigational therapy) before Day 1 of Cycle 1 for treatment of CRC General Medical Exclusions
• Malignancies other than CRC within 5 years prior to randomization, except for those with a negligible risk of metastasis or death
• Radiotherapy to any site for any reason within 28 days prior to Day 1 of Cycle 1
• Clinically detectable third-space fluid collections that cannot be controlled by drainage or other procedures prior to study entry
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to Day 1 of Cycle 1
• Lactating women
• Clinically suspected or confirmed central nervous system (CNS) metastases or carcinomatous meningitis
• Active infection requiring IV antibiotics
• Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs, inhaled corticosteroids, or the equivalent of less than or equal to (</=) 10 milligrams per day (mg/day) prednisone
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, or cirrhosis
• Sensory peripheral neuropathy greater than or equal to (>/=) Grade 2 Bevacizumab-Specific Exclusions
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of bevacizumab or an investigational drug or that may affect the interpretation of the results or render the participant at high risk for treatment complications
• Inadequately controlled hypertension
• Prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Class II or greater congestive heart failure (CHF)
• History of myocardial infarction or unstable angina within 6 months prior to Day 1
• History of stroke or transient ischemic attack (TIA) within 6 months prior to Day 1
• Significant vascular disease within 6 months prior to Day 1
• Evidence of bleeding diathesis or significant coagulopathy
• Current or recent (within 10 days of first dose of study treatment) use of aspirin or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol
• Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
• History of abdominal or tracheo-oesophageal fistula or gastrointestinal (GI) perforation within 6 months prior to Day 1
• Clinical signs or symptoms of GI obstruction or a requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
• Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
• Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture 5-Fluorouracil-Specific Exclusion
• Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene polymorphism predisposing the participant for 5-fluorouracil toxicity