An IFL regimen combining irinotecan, a bolus administration of 5-fluorouracil (5-FU) and leucovorin (LV) was associated with a significantly better response rate, progression-free survival and median overall survival, compared to 5-FU/LV against metastatic colorectal cancer. Despite a favorable initial report, randomized trials have suggested that triple therapy may be more toxic (severe neutropenia, diarrhea), leading to unacceptably high rates of early treatment-related mortality. On the other hand,a survival benefit for the oxaliplatin-containing regimen (FOLFOX 4) compared to bolus IFL, has been shown from INT trial 9741, and a European trial (V 308) suggests similar efficacy for combinations of irinotecan or oxaliplatin with short-term infusional 5-FU/LV (FOLFIRI or FOLFOX 6). Overall, FOLFIRI or FOLFOX regimen is now a standard option for first-line treatment of metastatic CRC.