BACKGROUND: We investigated the feasibility of a 16-week supervised heavy resistance training program with weekly undulating periodization for individuals with persistent non-specific low-back pain (LBP). METHODS: Twenty-five adults with persistent non-specific LBP participated in this mixed methods feasibility study. Participants trained a whole-body program consisting of squat, bench press, deadlift and pendlay row two times per week for 16 weeks. We assessed pain intensity, pain-related disability, pain self-efficacy and one-repetition maximum strength at baseline, 8 weeks and 16 weeks. Three focus group interviews were conducted at the end of the program. Linear mixed models were used to assess changes in outcomes, and the qualitative data was assessed using systematic text condensation. RESULTS: We observed clinically meaningful reductions in pain intensity after 8 and 16 weeks of training. The mean difference on the numeric pain rating scale (0-10) in the last 2 weeks from baseline to 8 weeks was 2.6 (95% CI: 1.8-3.6) and from baseline to 16 weeks 3.4 (95% CI: 2.5-4.4). In addition, there were improvements in pain-related disability (3.9, 95% CI: 2.3-5.5), pain self-efficacy (7.7, 95% CI: 5.4-10.1) and muscle strength. In the focus group interviews, participants talked about challenges regarding technique, the importance of supervision and the advantages of periodizing the training. Perceived benefits were improved pain, daily functioning, energy level and sleep, and changes in views on physical activity. CONCLUSION: Periodized resistance training with weekly undulating periodization is a feasible training method for this group of individuals with persistent non-specific LBP. A randomized clinical trial should assess the efficacy of such an intervention. TRIAL REGISTRATION: clinicaltrials.gov / Identifier - NCT04284982, Registered on February 24th 2020.