Objective: This study aims to investigate the feasibility, safety and efficacy of triplet regimen of neoadjuvant chemotherapy in patients with locally advanced resectable colon cancer.Methods: Patients with clinical stage IIIb colon cancer received a perioperative triple chemotherapy regimen(oxaliplatin 85 mg/m2 and irinotecan 150 mg/m2, combined with folinic acid 200 mg, 5-fluorouracil 500 mg bolus and then 2,400 mg/m2 by 44 h infusion or capecitabine 1 g/m2 or S-1 40–60 mg b.i.d orally d 1–10, repeated at 2-week intervals) for 4 cycles. Complete mesocolic excision was scheduled 2–6 weeks after completion of neoadjuvant treatment and followed by a further 6 cycles of FOLFOXIRI or XELOX. Primary outcome measures of this stage II trial were feasibility, safety, tolerance and efficacy of neoadjuvant treatment.Results: All 23 patients received neoadjuvant chemotherapy and underwent surgery. Twenty-one patients(91.3%) had reductions in tumor volume after neoadjuvant treatment, and 13 patients(56.5%) had grade 3–4toxicity. No patients had severe complications from surgery. Preoperative therapy resulted in significant downstaging of T-stage and N-stage compared with the baseline clinical stage including one pathological complete response.Conclusions: Neoadjuvant triple chemotherapy has high activity and acceptable toxicity and perioperative morbidity, and is feasible, tolerable and effective for locally advanced resectable colon cancer. Objective: This study aims to investigate the feasibility, safety and efficacy of triplet regimen of neoadjuvant chemotherapy in patients with locally advanced resectable colon cancer. Methods: Patients with clinical stage IIIb colon cancer received a perioperative triple chemotherapy regimen (oxaliplatin 85 mg / m2 and irinotecan 150 mg / m2, combined with folinic acid 200 mg, 5-fluorouracil 500 mg bolus and then 2,400 mg / m2 by 44 h infusion or capecitabine 1 g / m2 or S-1 40-60 mg bid orally d 1-10, repeated at 2-week intervals for 4 cycles. Complete mesocolic excision was scheduled 2-6 weeks after completion of neoadjuvant treatment and followed by a further 6 cycles of FOLFOXIRI or XELOX. Primary outcome measures of this stage II trial were feasibility, safety, tolerance and efficacy of neoadjuvant treatment. Results: All 23 patients received neoadjuvant chemotherapy and underwent surgery. Twenty-one patients (91.3%) had reductions in tumor volume after neoadjuvant treatment, and 13 Preoperative therapy resulted in significant downstaging of T-stage and N-stage compared with the baseline clinical stage including one pathological complete response. Conclusions: Neoadjuvant triple chemotherapy (56.5%) had grade 3-4 toxicity has high activity and acceptable toxicity and perioperative morbidity, and is feasible, tolerable and effective for locally advanced resectable colon cancer.