Background: Induction chemotherapy (CT) is a promising option in LARC. FOLFOXIRI + BV is an effective treatment in metastatic colorectal cancer. Methods: This is a phase II multicentric single-arm single-stage trial. Primary endpoint was 2-year disease-free survival (DFS). Patients (pts) with LARC at < 12 cm from the anal verge, cN+ or cT4 or high risk cT3 (MRI criteria) underwent 6 cycles of FOLFOXIRI (irinotecan 165 mg/m², oxaliplatin 85 mg/m², folinate 200 mg/m² and 5FU 3200 mg/m² in 48 h) + BV (5 mg/kg) every 2 weeks followed by CRT (50.4 Gy + 5FU 225 mg/m²/day or capecitabine 825 mg/m²/bid continuously + BV 5 mg/kg on days 1, 15, 28). Surgery was planned 8 weeks after CRT. Results: We enrolled 48 pts. Main characteristics were: median age, 53 years (30-74); cT2/T3/T4, 4%/60%/36%; cN0/N+, 4%/96%. 46 pts completed induction CT: 1 patient (pt) died due to bowel perforation and sepsis and 1 discontinued CT after acute kidney injury. Main grade (G) 3/4 toxicities during induction were neutropenia (42%), febrile neutropenia (4.2%), diarrhea (12.5%). Clinical Response Rate (CRR) after induction was 77%. One pt underwent surgery after induction CT and 45 started CRT. After the first 13 pts, the protocol was amended and the schedule of capecitabine modified (800 mg/m²/bid 5 days/week) due to an excessive rate of G3 hand-foot syndrome (23%) and proctitis (23%). After amendment all pts completed CRT with acceptable toxicity: in particular G3-4 toxicities included only 6.2% proctitis. CRR after CRT was 78%. One pt had early progressive disease (PD) after CRT and died. 44 pts underwent surgery: low anterior resection 90%, abdomino-perineal resection 7%. R0 resection was achieved in 98% of pts. Early (90 days) post-surgical complication rate was 31% with 17% of anastomotic dehiscences, all solved. Pathologic complete response rate was 36%. At a median follow up of 21 months, 8 pts had PD (2 local recurrences) and the estimated 2y-DFS is 78%. Conclusions: Induction CT with FOLFOXIRI + BV followed by CRT is feasible and highly active in LARC. The rate of early post-surgical complications is not negligible. Preliminary results for DFS are promising. Clinical trial information: 2011-003340-45.