To achieve effective bioleaching of base metals from PCBs, a balance of the rates of regeneration of ferric lixiviant and ferric reduction for leaching is required. We investigate the effect of Fe2+ concentration, PCB solid loading, and operating mode in a novel two-stage bioleaching reactor system comprised of a stirred tank reactor for Fe3+ leaching of base metals in PCBs, coupled to a packed-bed reactor with biomass retention for microbial Fe3+ regeneration. The packed-bed component consisted of multiple column reactors in series, each packed with polyurethane foam biomass support particles colonised with mixed copper-adapted mesophilic cultures of Leptospirillum ferriphilum, Acidithiobacillus caldus, and Acidiplasma cupricumulans. Enhanced tolerance to metal ions and protection offered by biofilm associated with colonised cells are used to maintain high microbial ferrous oxidation rates. The initial Fe2+ concentration was varied from 5–10 g/L, and PCB loading was varied from 0–20% w/v. Two operation modes were explored: (1) a fully closed-loop system where a metal ions-rich stream was re-circulated between the chemical and packed-bed bioreactor, and (2) an open system with part of the metal ion-rich stream re-circulated and part recovered for continuous metal recovery. At each reactor configuration studied, the Fe3+ reduction rate as a function of metal dissolution was compared to that of microbial Fe3+ regeneration rate. With the microbial Fe3+ regeneration being the rate-determining step in bioleaching, optimum reactor configuration for maximum delivery of the required Fe3+ oxidant is vital to maximise the space-time yield of the bioleaching to optimise overall bioleaching efficiency.