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Background: This study sought to evaluate the effect of postoperative chemoradiotherapy (CRT) in patients with locally advanced gastric cancer (LAGC) who respond poorly to neoadjuvant chemotherapy (ChT). Methods: The database of a tertiary medical center (2009-2019) was retrospectively reviewed for patients with LAGC in whom the initial treatment strategy consisted of perioperative ChT and surgery. Those who were subsequently referred for postoperative CRT because of a poor pathologic primary-tumor response (ypT3-4, ypN2-3, R1 resection) were selected for the study. CRT consisted of 45 Gy in 25 fractions of 1.8 Gy combined with capecitabine 825 mg/m² twice daily on radiotherapy days or continuous infusion of 5-fluorouracil 180 mg/m²/day. Intensity-modulated radiation was planned using computed tomography simulation. Results: The cohort included 26 patients of median age 61 years with LAGC (clinical stage IIA-III) after surgery with D1-D2 lymphadenectomy. R0 resection was achieved in 15 (58%). Pathological stage was III in 69% (IIA-IVA); 73% had pT3-T4 tumors, and 65%, N2-N3 disease. Nineteen patients (73%) also received adjuvant ChT (same as neoadjuvant or different regimen) before postoperative CRT. Treatment was well tolerated, except in one patient with grade 4 vomiting. During a median follow-up time of 29 months (9-140 months), recurrences were documented in 14 patients (54%): 5 regional, 7 distant, 2 combined. Median progression-free survival was 23 months (10-140 months), and median overall survival was not reached. Estimated 5-year survival rates were 42% and 53%, respectively. Conclusions: This small retrospective study suggests that in patients with LAGC who show a poor pathologic response to neoadjuvant ChT, a good outcome relative to reference arms in randomized trials can still be achieved with the addition of postoperative CRT. Further studies of the benefit of a tailored adaptive treatment approach to LAGC based on the response to neoadjuvant ChT are warranted.