This study explored the effect of symptom-based individualized nutritional intervention on chemotherapy tolerance and quality of life (QOL) in patients with colorectal cancer (CRC) undergoing postoperative chemotherapy. Postoperative patients with CRC (n = 88) were randomly assigned to the control group (CG, n = 45) and intervention group (IG, n = 43) receiving conventional diet counseling and symptom-based individualized nutritional intervention, respectively, and chemotherapy tolerance, adverse effects, and QOL were compared. Participants in the IG exhibited better nutritional status at the last chemotherapy cycle, with lower Nutrition Risk Screening 2002 (2.37 ± 0.65 vs. 3.78 ± 0.65, p < 0.01) and Patient-Generated Subjective Global Assessment (6.26 ± 0.76 vs. 7.78 ± 0.70, p < 0.01) scores. Compared with CG, relative dose intensity reduction (9.3% vs. 25.89%, p = 0.02), chemotherapy regimen change (25.58% vs. 53.33%, p < 0.01), and chemotherapy delay (13.95% vs. 35.56%, p = 0.019) were lower in the IG. Nausea/vomiting (2.33% vs. 17.78%, p = 0.017), thrombocytopenia (2.33% vs. 28.89%, p < 0.01), and hand-foot syndrome (4.65% vs. 22.22%, p = 0.03) were less frequent in the IG. Participants in the IG had better QOL, with higher physical function scores at cycles 4 (67.91 ± 5.22 vs. 62.22 ± 4.02, p < 0.01) and 8 (72.71 ± 6.31 vs. 57.63 ± 4.75, p < 0.01). Individualized nutritional interventions improved chemotherapy tolerance and QOL and reduced adverse effects in this patient cohort.