Background: IV chemotherapy (chemo) downsizes LM-CRC in most pts. Yet less than 15% of those with previously unresectable LM and prior chemo undergo successful complete macroscopic LM resection (R0-R1). 4-y survival is 42% in all pts with LM resection (Livermetsurvey). Purpose is to determine disease-free survival (DFS) and OS in pts with R0-R1 partial hepatectomy after neoadjuvant HAI of irinotecan, oxaliplatin, and 5-fluorouracil and IV-CET for LM-CRC in the first multicenter trial testing this strategy. Methods: The 9 centers accrued 64 pts with 1-3 prior chemo, bilateral LM (84% pts), a median number of 10 LM, with largest diameter of 53 mm, spread in a median of 6 segments. First intent LM surgery was deferred for high LM number (72% of the pts), large size (69%), ill location (61%), extra-hepatic disease (2%), or other cause (12%). Liver surgery was performed whenever R0-R1 became feasible at q6-9 weeks multidisciplinary review. Results: LM surgery occurred 2.6 to 19.4 months (mo) after inclusion (median, 5.3). Single-, two- or three-stage R0-R1 hepatectomies were performed in 15, 3 and 1 pt respectively. LM resection was associated with younger age (median, 52 vs 60 y, p=0.01), less liver involvement (≤25% vs >25% tumor replacement, 68% vs 38% of the pts, p=0.025; median N of segments involved, 5 vs 7, p=0.015), and 1 rather than 2-3 prior chemo (46% vs 20% of the pts, p=0.01). Resection rate did not differ according to sex, PS, primary tumor stage or grade, LM bilaterality and number, prior resections, extrahepatic disease, or objective response rate (42% vs 40%). Median DFS was 15.7 mo [95% CI, 10- 21], with LM recurring in 11 pts (58%). Median OS was 18.7 mo [13-24] with no 4-y survivor among the 45 pts without LM resection. In contrast, median OS was 35 mo [31-40] in the 19 resected patients, with 45% [10.3 - 79.7] survival at 4-y (p<0.001). Conclusions: The combination of IV-CET with HAI-IFO deserves upfront evaluation as a most effective neoadjuvant treatment option within a medico-surgical strategy aiming at the eradication of LM-CRC. Clinical trial information: NCT00852228.