Background: N is a multiple angiokinase inhibitor (including VEGFR, PDGFR and FGFR). A randomised Phase III study, LUME-Colon 1 (NCT02149108), evaluated the efficacy and safety of N in pts with refractory mCRC after failure of standard therapies. LUME-Colon 1 showed a statistically significant improvement in PFS (HR [95% CI] 0.58 [0.49–0.69]; p < 0.0001) but no difference in OS (HR [95% CI]: 1.01 [0.86–1.19]; p = 0.8659). Here, we report the HRQoL outcomes. Methods: 768 pts with mCRC adenocarcinoma refractory to standard chemotherapy were randomised 1:1 to receive either N (200 mg bid) + BSC or P (bid) + BSC in 21-day courses until disease progression or undue toxicity. HRQoL was assessed every 21 days using the EORTC QLQ-C30 instrument; the main endpoints of interest were the differences in mean scores up to median follow-up time (treatment difference, TD) for physical functioning (PF) and global health status/QoL (QL) scales using a longitudinal model, with 95% CIs and associated p-values adjusted for baseline stratification factors. Time to deterioration (TTD) of scores and status change ( ≥ 10 point change from baseline) were also assessed. Results: Compliance with questionnaire completion was high ( > 85% in first 12 cycles). Mean baseline (N vs P) PF (80 vs 80) and QL (65 vs 65) scale scores were balanced between treatment arms. The mean TD favoured N vs P for PF scale scores (TD 2.66 [95% CI: 0.97–4.34]; p = 0.0020) and QL scale scores (TD 1.61 [95% CI: −0.04–3.27]; p = 0.0555). TTD of PF (HR 0.84; 95% CI: 0.69–1.03; p = 0.0904) and QL (HR 0.90; 95% CI: 0.75–1.08; p = 0.2674) scores were not significantly different between treatment groups, although the percentage of patients with improved PF (17.2% vs 11.8%; p = 0.0462) and QL scores (30.3% vs 21.6%: p = 0.0102) were both significantly higher for N vs P. Conclusions: In LUME-Colon 1, patient reported outcomes confirmed that overall HRQoL was not impaired by treatment with N. There was evidence for improvement of PF and QL with N vs P, corresponding to the significant increase in PFS observed. Clinical trial information: NCT02149108