Background: In our principle, hepatectomy is the first choice for liver metastases (mets) from colorectal cancer whenever future remnant liver is over 40% in volume. Recently, FOLFOXIRI (5-FU/LV+Oxaliplatin+Irinotecan) plus bevacizumab (Bev) regimen was reported to be high rates of pathologic responses and necrosis of colorectal liver metastases (CLMs) without increasing liver toxicity (Br J Cancer 2013). The aim of this retrospective study is to clarify impact of FOLFXIRI plus molecular targeted drugs on initially unresectable CLMs. Methods: Among 81 patients with initially unresectable liver mets, 59 had chemotherapy (CTx), including 10 old CTx (-2003) and 49 new CTx (2004- ) using new drugs such as oxaliplatin. Regimen of FOLFOXIRI + molecular target drugs, consisting of Bev in 12 and C/P-mab in 2, was applied to 14 patients. “Conversion” rate and the period until “Conversion”, and overall survival (OS) were compared between FOLOFOXIRI group and other regimen group. Pathological and morphological responses were also examined. Results: “Conversion” was not obtained in old CTx group. In new CTx group, “Conversion” was achieved in 21 patients (43%). OS in “Convresion” group was better than “non-conversion” group (3-year survival: 70 % vs. 15 %). “Conversion” rate in FOLFOXIRI group was higher than that in other regimen group (64% vs. 34%). The period until “Conversion” in FOLFOXIRI group was shorter than that in other regimen group (6.2 cycles vs. 16.1 cycles). Furthermore, tumor necrosis rate in FOLFOXIRI group (80 %) was higher than that in other regimen group (47 %), and morphologic response (optimal/partial) in FOLFOXIRI group (33 % / 44 %) was higher than in other regimen group (8 % / 33 %). Prognosis after “Conversion” in FOLFOXIRI group was better than that in other regimen group (3-year survival: 80 % vs. 33 %). In addition, time to surgical failure (TSF) in FOLFOXIRI group tended to be better than that in other regimen group. Conclusions: FOLFOXIRI + molecular target drugs is highly effective in order to obtain early conversion and better long-term outcome after ”Conversion” for initially unresectable CLMs.