The addition of oxaliplatin and irinotecan to 5-FU improves tumor response rate and progression-free survival in patients with advanced colorectal cancer compared with 5-FU alone, but increases toxicity. It is not clear whether such combination therapies (5-FU+oxaliplatin or 5-FU+irinotecan) should be systematically used as first line treatment or as second line treatment after 5-FU failure.