Objective To investigate the short- and long-term efficacy of the neoadjuvant regimen of irinotecan + 5-Fu / Lv combined with short course intensive hyperfractionated radiotherapy in the treatment of low rectal cancer. Methods A total of 130 patients with low rectal cancer from October 2015 to October 2018 were enrolled. The patients were divided into a neoadjuvant treatment group(n = 61) and a control group(n = 65) by using random number table method. The neoadjuvant group received irinotecan+5-Fu / Lv combined with 25Gy (5×5) radiotherapy. Efficacy was evaluated after 6 weeks of treatment. The patients were treated with surgery or follow-up according to the results. The control group underwent the total mesorectal excision (TME) surgery directly. Patients with stage Ⅱ and Ⅲ in both groups received 6 cycles of chemotherapy and were followed up for 5 years. Results The anal preservation rate of patients in the neoadjuvant group with tumors <5 cm from the anal verge was 71. 4% , which was significantly higher than 45. 0% of the control group ( P < 0. 05). The R0 removal rate in both groups was 100% . The incidence of grade 3 diarrhea was higher in the neoadjuvant group (P<0. 05). There was no significant difference in the incidence of anastomotic leakage between the two groups ( P >0. 05). The 3-year disease-free survival (DFS) rate and 5-year overall survival (OS) rate of the neoadjuvant group were better than those of the control group. However, the subgroup analysis of stages showed that only stage I had a significant difference, while stages II and III had no statistical significance. Multivariate analysis showed that the treatment methods had no significant effect on the overall survival rate. Conclusions This neoadjuvant regimen is safe and effective. It can improve the sphincter-preservation rate and significantly enhance the 5-year OS of patients with stage Ⅱ and Ⅲ low rectal cancer.