This is a phase 2, multicenter, randomized, double-blind, double-dummy, placebo-controlled, three-arm trial to be conducted in the United States, Europe, and Asia. Approximately 150 eligible KRAS-mutant metastatic colorectal cancer subjects who have failed first line fluoropyrimidine and oxaliplatin-based regimen with or without anti-VEGF therapy will be randomized in a 1:1:1 ratio to receive AMG 479 placebo plus AMG 655 with FOLFIRI, or AMG 479 plus AMG 655 placebo with FOLFIRI, or AMG 479 placebo plus AMG 655 placebo with FOLFIRI

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of colon or rectum in patients with metastatic disease
• Mutant-type KRAS tumor at screening
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 1
• Adequate hematology, renal, hepatic, and coagulation function

Exclusion Criteria:

• History or known presence of central nervous system metastases
• History of other malignancy
• Prior irinotecan-based chemotherapy for advanced/metastatic disease
• Prior death receptor agonists, or other systemic IGF-1R agonists in any setting
• Uncontrolled cardiovascular disease