According to Eurostat, the agricultural sector is by far the biggest producer of the residual biomass in Europe, annually generating ca. 400 million tonnes (Mt) of dry agricultural waste. This residual biomass is usually either utilized for low value applications (compost or animal feed) or have to be deactivated to be safely disposed. On the other side, this residual biomass is highly rich in various bioactive compounds (oils, fatty acids, polyphenols, proteins) which could be used to improve the human health and wellbeing but usually lost for high-value applications due to the lack of comprehensive technology to effectively extract and preserve the bioactives. Among the natural bio-based compounds, polyphenols is the biggest class of bioactives with a range of beneficial properties for human health which have not be utilized for their full potential. PHENOLEXA project proposes to unlock the potential of polyphenols-rich agri-side streams (olive, grape shoots and leaves, chicory and onion residues) to procure bioactive compounds of high value via the development of cascade smart biorefinery which combines pretreatment of the biomass with benign environmentally friendly green solvents extraction technology. PHENOLEXA will focus on the processing of several types of agri and biowaste to create a pool of new functional polyphenolic bioactives with the tuned functionality (anticancer, antiviral, anti-oxidant, antimicrobial, antifungal, anti-inflammatory) whereas the remaining fibres and colorants will be utilised in functional foods. PHENOLEXA will demonstrate the technology of the bioactive ingredients procurement at TRL4/5 and will create lab scale prototypes of cosmetic, nutraceutical, pharma and functional food products with their proved efficacy by the end of the project. PHENOLEXA will also validate the techno-economic feasibility and environmental sustainability of the proposed biorefinery.