This randomized, multicenter, open label study will evaluate the safety and efficacy of RO5083945 in combination with FOLFIRI as compared to FOLFIRI plus cetuximab or FOLFIRI alone as second line treatment in patients with metastatic colorectal cancer. Patients will be randomized to receive RO5083945 (1400 mg intravenously on Day 1 and Day 8 and every 2 weeks thereafter) plus FOLFIRI standard iv chemotherapy or FOLFIRI plus cetuximab (400 mg/m2 iv on Day 1 followed by 250 mg/m2 iv every week) or FOLFIRI alone. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Carcinoma of the colon and/or rectum
• Disease progression during or within 6 months of last dose of oxaliplatin containing first-line combination therapy for metastatic disease
• ECOG performance status 0-1
• Adequate hematological, renal and liver function

Exclusion Criteria:

• Prior treatment with monoclonal antibody/small molecule against epidermal growth factor receptor (EGFR)
• Prior treatment with irinotecan
• Radiotherapy within the last 4 weeks before first dose of study drug (except for limited field palliative radiotherapy for bone pain relief)
• CNS metastasis
• History of or active autoimmune disorders/conditions