BACKGROUND: Kohne et al. [Ann Oncol 2002;13:308-317] showed that four prognostic variables can be used to classify patients with metastatic colorectal cancer (CRC) treated with 5-fluorouracil (5-FU)/leucovorin (LV) into three risk groups with different overall survival (OS). This model was applied to data from phase II/III trials of first-line bevacizumab plus 5-FU/LV with/without irinotecan (IFL). METHODS: Data on tumor sites, Eastern Cooperative Oncology Group performance status, alkaline phosphatase levels and white blood cell counts were used to classify patients into Kohne prognostic high-, intermediate- and low-risk groups. Median OS and progression-free survival (PFS) were calculated for patients receiving 5-FU/LV plus bevacizumab or placebo (n = 489) and IFL plus bevacizumab or placebo (n = 812). RESULTS: Median OS was longer in 5-FU/LV/bevacizumab (11.2-22.6 months) than in the 5-FU/LV/placebo (5.7-17.5 months), and in the IFL/bevacizumab arm (14.3-22.5 months) than in the IFL/placebo arm (8.4-17.9 months) across the Kohne high-, intermediate- and low-risk groups. The addition of bevacizumab also extended median PFS across the Kohne risk groups compared with placebo. CONCLUSIONS: Bevacizumab improves OS and PFS across the Kohne risk classification in patients with metastatic CRC. The Kohne model can be extended to patients treated with 5-FU/LV/bevacizumab, IFL and IFL/bevacizumab and to PFS data.