This study is a Phase 1 and pharmacologic open-labeled dose-escalation trial using a "3+3" design exploring weekly, bi-weekly, and tri-weekly dosing schedules. Successive MM-151 monotherapy cohorts of three or more patients will be treated at escalating doses until a maximum tolerated dose is identified, and subsequently in combination with irinotecan. The study consists of three parts as follows: MM-151 monotherapy dose escalation (Part 1); MM-151 monotherapy expansion cohort in cetuximab-refractory colorectal cancer (Part 2); MM-151 + irinotecan dose escalation (Part 3). It is expected that approximately 4 study sites will participate.