Microbial fuel cells (MFCs) exploit the metabolic activity of electroactive microorganisms for oxidation of organic compounds and extracellular electron transfer to an external electrode. the technology is associate with very slowreaction rates, resulting in low current densities. Anodes with high specific surface should be used to increase the overall electricity generation. Carbon-based 3D materials, with high surface per unit of volume, are largely used anode materials in MFCs, although may show significant lack in efficiency due to mass transfer limitations, concentration gradients, velocity distribution and resistivity of the material. Consequently, the concomitant effect of several parameters should be assessed and quantified to design highly performing MFCs implementing 3D anode materials. In this work, miniature MFCs with 3D anodes are mathematically modelled to quantify the effect of operative parameters on performance. The model combines equations of charge conservation, mass transport phenomena, hydrodynamics, and kinetics of the involved processes under transient conditions, and provides 3D profiles with time of velocity, biofilm thickness, substrate concentration, current density and potential. The solution predicts a laminar flow, as it was expected with the low flow rates used. The concentration profiles show the consumption of substrate in the anode, with low values of local concentrations depending on organic load in the feed stream. The model also provides a versatile tool to optimise the operative conditions of the system, managing the flow arrangements to maximise either substrate removal or electricity generation.