Introduction:Upfront neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy remained a standard of care for locally advanced rectal cancers. However this strategy is associated with high rates of distant failure. Total neoadjuvant therapy with short course radiation therapy (SCRT) followed by full course of chemotherapy is investigated to assess toxicity&feasibility. Patients and methods: Fifty-one patients with locally advanced rectal cancer who presented to the National Cancer Institute (NCI), Cairo University, in the period from March 2018 to December 2020 were enrolled. Patients were assigned to neoadjuvant short course radiation therapy (25 Gy/ 5 fractions/1 week), then 2 weeks from the end of radiation they were commenced to full course chemotherapy CAPOX (capecitabine1000 mg/m2 BID, D1-14 and oxaliplatin 130 mg/m2 D1) for 6 cycles, followed by surgery within 4-6 weeks from the last chemotherapy cycle. Type of surgery was decided upon surgeon’s discretion. Results: All patients completed their planned radiation therapy. Only 1 patient had grade III radiation related diarrhea. Forty three patients completed their planned chemotherapy course, 8 patients had grade III diarrhea. As regard hematological toxicity, 6 patients developed grade 3 toxicity and only one patient developed grade 4 toxicity.