The best management choice in colorectal cancer patients with unresectable liver-only metastases should be represented by conversion chemotherapy aiming to reduce liver cancer deposits, thereby permitting curative surgery. Forty-eight consecutive stage IV colorectal cancer patients were treated with different chemotherapeutic regimens including biological drugs. Objective responses to chemotherapy were seen in 27 patients (56.2%; 95% CI 42.1-70.2%). Four patients (8.3%) showed complete response, 23 patients (47.9%) partial and 13 patients (27.1%) stable response. Eight patients (16.7%) progressed. The conversion rate was 35.4% (95% CI 21.8-48.9%) with 17 patients suitable for liver resection. Four complete responder patients refused surgery. The remaining 13 patients underwent curative hepatic resection (resection rate 27.1%; 95% CI 14.5-39.6%). The likelihood of a successful conversion chemotherapy appeared significantly related to the best response and to the K-Ras status. Wild-type K-Ras patients undergoing cetuximab therapy showed the best conversion rate. The four-year survival rate was significantly enhanced in converted compared to non-converted patients (57.1 and 0%, respectively), and in resected compared to non-resected patients (53.3 and 10.1%, respectively). Synchronous metastases and no conversion were shown to be the only covariates independently associated with a poorer long-term outcome. The possibility of curative liver surgery significantly prolongs outcome for colorectal cancer patients with unresectable liver-limited metastases. Prospective randomized trials are required to define the conversion rates with biological drugs.