Background: The standard therapy for the locally advanced rectal cancer (LARC) (Ra or Rb, T2Npsitive, T3/4Nany) is chemoradiotherapy (CRT) followed by surgery. The CRT prevents local recurrence, although problems such as complications or the improvement of distant recurrence still remain. Several studies about the neoadjuvant chemotherapy (NAC) without radiation showed favorable R0 resection rate and outcome, however the best regimen of NAC is unclear. The aim of this study is to investigate the efficacy and safety of mFOLFOXIRI and CAPOX/SOX as NAC. Methods: We examined the patients (pts) with LARC who were planned to receive mFOLFOXIRI (5FU 2400mg/m²/day1-2, leucovorin 200mg/m², oxaliplatin 85mg/m², irinotecan 150mg/m², every 2 weeks) or CAPOX/SOX(capecitabine 2000mg/m2 or S-1 mg/m2 80day1-14, oxaliplatin 130mg/m², day1, every 3weeks) for 8-12 weeks as NAC, retrospectively. Results: Forty-nine pts received mFOLFOXIRI and thirty-two pts received XELOX/SOX between Jan 2015 and Mar 2019. The characteristics of mFOLFOXIRI and XELOX/SOX were as follows; median age, 64 (37-80) and 65 (33-68); PS 0/1, 46(94%)/3(6%) and 14(44%)/18(56%); Ra/Rb-P, 4(8%)/45(92%) and 0/32; clinical T2/3/4, 4(7%)/27(55%)/19(39%) and 1(3%)/18(56%)/13(41%); clinical N0/1/2, 13(27%)/26(53%)/10(20%) and 7(22%)/17(53%)/8(25%). The pathological response rate which was defined as tumor affected area over one-third were 61.2% in mFOLFOXIRI and 65.6% in CAPOX/SOX including complete remission of 4.1% and 12.5%, respectively. Six of 49 pts withdrew from mFOLFOXIRI due to toxicities, whereas one of 32 pts from CAPOX/SOX. One pt received CRT after SOX because of lack of efficacy. The major grade 3/4 toxicities of mFOLFOXIRI were neutropenia (n = 22, 45%), thrombocytopenia and febrile neutropenia (n = 4, 8%) and anorexia (n = 3, 6%), whereas CAPOX/SOX neutropenia (n = 3. 9%), thrombocytopenia (n = 1, 3%) and hand-foot syndrome (n = 1, 3%). The one year of relapse free survival rate were 85.4% and 83.6%. Conclusions: Although the pathological response of mFOLFOXIRI was comparable with CAPOX/SOX, CAPOX/SOX was less toxic.The further investigation including 5 year overall survival rate rate was needed.