Objectives: Bevacizumab is a monoclonal antibody that directly inhibits vascular endothelial growth factor, a key regulator of angiogenesis. Bevacizumab significantly improves progression-free and/or overall survival in metastatic colorectal cancer in combination with standard chemotherapy. This review describes the evolution of irinotecan-based regimens for metastatic colorectal cancer and evaluates the addition of bevacizumab to these regimens. Methods: Literature searches from large publication databases (PubMed, ASCO, ASCO GI, ESMO) were performed to capture key data relevant to bevacizumab, irinotecan, and the treatment of colorectal cancer. Results: Data from numerous large, multinational studies support the addition of bevacizumab to irinotecan-containing chemotherapy regimens for further improvement in patient outcomes. In a randomized, placebo-controlled trial, addition of bevacizumab to irinotecan significantly improved progression-free survival, overall survival and response rate in patients with metastatic colorectal cancer, and these results are supported by a number of other clinical trials and observational studies. Furthermore, the addition of bevacizumab to irinotecan improves outcomes regardless of K-ras mutational status. Bevacizumab has a well-established safety profile and the toxicities associated with its use are usually mild in severity and easily manageable. Conclusions: Addition of bevacizumab to irinotecan-containing regimens is an effective therapy option for the treatment of metastatic colorectal cancer. Copyright (C) 2010 S. Karger AG, Basel